Synthesis, isolation, identification and characterization of new process-related impurity in isoproterenol hydrochloride by HPLC, LC/ESI-MS and NMR

Abstract

One unknown impurity (Imp-II) during the analysis of laboratory batches of isoproterenol hydrochloride was detected in the level ranging from 0.04% to 0.12% by high performance liquid chromatography with UV detection. The unknown impurity structure was proposed as 4-[2-(propan-2-ylamino)ethyl]benzene-1,2-diol (Imp-II) using the liquid chromatography--mass spectrophotometry (LC--MS) analysis. Imp-II was isolated by semi-preparative liquid chromatography from the impurity-enriched reaction crude sample. Its proposed structure was confirmed by nuclear magnetic spectroscopy such as 1H, 13C, DEPT (1D NMR), HSQC (2D NMR) and infrared spectroscopy (IR), and retention time and purity with HPLC followed by the chemical synthesis. Due to less removable nature of Imp-II during the purification, the synthetic process was optimized proficiently to control the formation of Imp-II below to the limit<0.12% in the course of reaction. The new chemical route was developed for the preparation of this impurity in required quantity with purity to use as reference standard. The most probable mechanism for the formation of Imp-II was discussed in details.

New approaches to identification and characterization of tioconazole in raw material and in pharmaceutical dosage forms

“…4). The DEPT 135 experiment enabled the classification of the carbon types present [37]. Eleven peaks were observed (2 with negative intensity corresponding to two carbons CH 2 , and 9 with positive intensity due to CH carbons, only one of which has hybridation sp 3 at 76.39 ppm), and the remaining five peaks of the 13 C spectrum were quaternary carbons.

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Chitosan-hydroxypropyl methylcellulose tioconazole films: A promising alternative dosage form for the treatment of vaginal candidiasis

“…The ATR-FTIR spectrum of CH ( Figure 2Ab) showed a typical band between 3000-3600 cm -1 , concerned with -OH groups, which is broad due to overlapping with the stretching band of -NH (Pawlak and Mucha, 2003). Other bands were also observed centered at: 2925 cm -1 (stretching vibration of C─H bond); 1643cm -1 (amide I); 1595 cm -1 (NH 2 bending) (Tejada et al, 2017b); 1418 cm -1 (carboxyl -COOH) (Li et al, 2005); 1326 cm −1 (Amide III) (Kumar et al, 2017); 1150 cm -1 (stretching of the C-O-C bridge); 1060 cm -1 and 1020 cm -1 associated to the C-O stretching vibration (Espinosa-Andrews et al, 2010); and finally the band at 892 cm -1 assigned to the absorption peaks of β-(1,4) glycosidic unions in CH (Yue et al, 2009).…”

A Review: Recent Trends in Analytical Techniques for Characterization and Structure Elucidation of Impurities in the Drug Substances

“…Different techniques for impurity profiling, include coupling of CE with varying MS ionization systems such as electrospray ionization (ESI-MS), atmospheric pressure chemical ionization (APCI-MS), atmospheric pressure photoionization (APPI-MS) and thermospray ionization (TSI-MS). The ESI-MS and TSI-MS are useful for detecting the ionic compound whereas; the APCI-MS and APPI-MS are not capable of detecting the ionic sample [66][67][68][69][70][71][72] . Accordingly, it can be also aid to differentiate between the ionic or non-ionic unknown impurity.…”